Hydrochlorothiazide

Is hydrochlorothiazide safe?

For most people, yes. Hydrochlorothiazide, usually shortened to HCTZ, is a thiazide diuretic (a "water pill") that has treated high blood pressure in the United States since February 1959. It was still the 18th most prescribed US medicine in 2024, with about 32 million prescriptions (ClinCalc). There is no boxed warningBoxed warningThe strongest safety warning the US FDA puts on a medicine's label, printed inside a black border at the top.More in the glossary, no dependence and a wide margin in overdose. We score it 83.

The catch is that HCTZ works by making the kidneys flush out salt and water, and that can pull sodium and potassium too low. Older people starting it are most at risk. Two newer issues matter for long-term users: a small rise in skin cancer, and photosensitivity.

Low sodium and potassium: the main risk

Thiazides are the most common cause of drug-induced low sodium (hyponatraemia). A Swedish study of 11,213 hospital admissions, published in 2021, found thiazide diuretics accounted for 27% of admissions for low sodium. The risk was highest straight after starting, about 48 times higher in the first weeks, and fell to about 3 times after 13 weeks. Confusion, drowsiness, nausea, unsteadiness and falls can all be signs.

Potassium is the other mineral to watch. The label says doses above 50 mg a day are often associated with marked drops. Low potassium causes muscle cramps and weakness and, in severe cases, heart rhythm problems, especially in people on digoxin. HCTZ also increases magnesium loss in the urine, and it can raise calcium, uric acid (bringing on gout) and blood sugar.

This is why doctors check blood tests a few weeks after starting and then from time to time. If you are told to take potassium or magnesium, the dose should come from them, because too much potassium is dangerous with ACE inhibitors and ARBs.

The skin cancer warning

In 2018 the UK regulator, the MHRA, warned that HCTZ raises the risk of non-melanoma skin cancer. Two Danish national studies found a dose-dependent link: with the highest cumulative use, the odds of squamous cell carcinoma were about 7 times higher and of basal cell carcinoma about 1.5 times. The MHRA's best estimate was a 7.7-fold rise in squamous cell carcinoma after 25 mg a day for 22 years. Other blood pressure drugs, including the thiazide bendroflumethiazide, did not show the same link. HCTZ's photosensitising effect is the likely mechanism.

The FDA approved similar US labelling in 2020, based on its own Sentinel study. In absolute terms the risk is small: about 1 extra squamous cell cancer per 16,000 users a year, and about 1 per 6,700 a year for white patients who have taken 50,000 mg in total (about five and a half years at 25 mg a day). For most people the blood pressure benefit is much larger. Sun protection and regular skin checks are sensible, and people who have already had skin cancer should ask their doctor whether another drug would suit them better.

Interactions to know

Combined with	What can happen
Lithium	Diuretics reduce lithium clearance and add a high risk of lithium toxicity; the label says they generally should not be given together
NSAIDs such as ibuprofen	Weaker blood pressure and diuretic effect; extra kidney strain with ACE inhibitors or ARBs
Digoxin	Low potassium makes digoxin toxicity more likely
Steroids such as prednisone	More potassium loss
Diabetes medicines	Blood sugar may rise and doses may need changing
Cholestyramine, colestipol	Absorption of HCTZ falls by up to 85% and 43%
Alcohol, opioids, barbiturates	More dizziness on standing

HCTZ is often combined with lisinopril or losartan in a single tablet. These combination labels carry a boxed warningBoxed warningThe strongest safety warning the US FDA puts on a medicine's label, printed inside a black border at the top.More in the glossary about harm to an unborn baby, which comes from the ACE inhibitor or ARB, not from HCTZ.

Who should be careful

• Older adults, especially in the first month, because of low sodium and falls.
• Anyone taking lithium or digoxin.
• People with gout, diabetes, severe kidney disease or liver cirrhosis.
• People with an allergy to sulfonamide ("sulfa") drugs, in whom the label contraindicates HCTZ.
• People with a history of skin cancer or heavy sun exposure.
• Anyone who suddenly gets eye pain or blurred vision in the first weeks, which can be acute angle-closure glaucoma and needs urgent care.

Hot weather, vomiting or diarrhoea make dehydration more likely. If you are unwell and cannot keep fluids down, talk to your doctor or pharmacist about what to do with your water pill.

How we scored it

Dependence (98) and track record (95) are strong, and overdose marginOverdose marginHow far a normal dose is from a harmful one. A wide margin means an accidental extra dose is unlikely to cause serious harm.More in the glossary (88) is wide. Serious side effects (75) is the weakest weighted factor because low sodium and potassium send a real number of older people to hospital, while interactions (70) reflects lithium and the NSAID combination, and regulatory warnings (78) the skin cancer labelling.